Transdermal drug delivery systems can be categorized into three general types. The earliest devices have a simple two-layer "Band-Aid" configuration composed of a backing layer coated with adhesive. Usually the drug is mixed in the adhesive layer that fixes the bandage to the skin. These medicated bandages bring a known quantity of drug to a known area of skin for a known period of time, but have no mechanism for controlling the rate at which the drug is delivered to the patient.
The second type of device, in this context referred to as a monolithic system, is a system incorporating a backing layer, a matrix layer, and an adhesive layer. The matrix layer is made of a polymer material in which the solid drug is dispersed and the rate at which the drug is released from the device is controlled by the polymer matrix. With this type of system, the drug release rate falls off with time as the drug in the skin-contacting side of the matrix is depleted.
This type of transdermal drug delivery system is exemplified by the development and marketing of nitroglycerin-releasing transdermal therapeutic system (Nitro-Dur by Key), which has been approved by the FDA for once-a-day medication of angina pectoris.
The third type of device is the reservoir system. In this case, the drug is contained in a reservoir seperated from the skin by an inert polymeric membrane that controls the rate, at which drug is delivered to the skin. These devices offer an important advantage over the monolithic geometry because as long as the drug solution in the reservoir remains saturated, the drug release rate through the membrane is constant.
The rate of drug release from this type of transdermal drug delivery system can be tailored by varying the polymer composition, the permeability coefficient, and/or the thickness of the rate-controlling membrane and adhesive. Several transdermal therapeutic systems have been successfully developed from this technology and are best exemplified by the development and marketing of a nitro-glycerin-releasing transdermal therapeutic system (Transderm-Nitro by Ciba), which has been approved by the U.S. Food and Drug Administration (FDA) for once-a-day medication of angina pectoris a scopolamine-releasing transdermal therapeutic system (Transderm-Scop by Ciba) for 3-day protection from motion sickness and a clonidine-releasing transdermal therapeutic system.
A fourth type of device is a microreservoir-type drug delivery system. In this approach, the drug reservoir is formed by first suspending the drug solids in the aqueous solution of a water-soluble polymer (e.g. polyethylene glycol) and then dispersing the drug suspension homogeneously in a lipophilic polymer, by high-shear mechanical force, to form thousands of unleachable, microscopic spheres of drug reservoirs. This thermodynamically unstable dispersion is quickly stabilized by immediately cross-linking the polymer chains in situ, which produces a medicated polymer disc with a constant surface area and a fixed thickness. A transdermal therapeutic system is then produced by positioning the medicated disc at the center of an adhesive pad. This technology has been successfully utilized in the development and marketing of a nitroglycerin-releasing transdermal therapeutic system (Nitrodisc by Searle) that has been approved by the FDA for once-a-day treatment of angina pectoris.
The pattern of drug release from the device is important. If drug is delivered to the skin at a rate less than the maximum rate at which it can be absorbed by the skin, the device is the primary dosage controlling mechanism. When drug is delivered to the skin faster than the skin can absorb it, the skin surface is then saturated with drug at all times, and the limiting factor for systemic dosage is the rate of absorption through the skin.
As the skin is substantially impermeable to most drugs the delivery rate is controlled by the skin in most real systems. One approach to solve this problem is to administer a permeation enhancer alongside with the drug. These enhancers can be used in the new system according to the present invention as well as in the old systems.